Doenjang (Traditional Korean Fermented Soy Paste) Attenuates Development of Colitis-Associated Colorectal Cancer by Modulating Apoptotic, Inflammatory, and Gut Microbiota Pathways

Colitis-associated colorectal cancer (CAC) is a type of colorectal cancer (CRC) that develops as a result of chronic inflammation, particularly in patients with inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. Persistent intestinal inflammation and dysbiosis of gut microbiota under these conditions are major contributors to CRC progression. <i>Doenjang</i>, a traditional Korean fermented soybean paste, contains probiotics that influence intestinal microbiota composition, as well as biogenic amines (BAs), harmful compounds generated during fermentation. We analyzed the bacterial composition and BA content of <i>Doenjang</i> and evaluated its effects on CAC in a mouse model of AOM/DSS-induced CAC. Results revealed that <i>Doenjang</i> contains diverse beneficial probiotics alongside BAs. <i>Doenjang</i> significantly reduced tumor formation and attenuated CAC progression by modulating inflammatory and apoptotic pathways and suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) by inhibiting the NF-κB pathway. Additionally, <i>Doenjang</i> restored intestinal epithelial barrier integrity by increasing the expression of mucin-related genes (MUC-2, MUC-3) and protective factors like TFF-3. Gut microbiota analysis revealed that <i>Doenjang</i> promoted a healthier gut environment by increasing microbial diversity and reducing inflammation-related bacterial populations. These findings suggest that <i>Doenjang</i> helps prevent and manage CAC by modulating inflammatory responses and gut microbiota composition.